Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbens
Abstract Recent research has suggested that the mesolimbic dopamine network that mainly terminates in the nucleus accumbens may positively control the peripheral immune system. The activation of dopamine receptors in neurons in the nucleus accumbens by the release of endogenous dopamine is thus expe...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Molecular Brain |
| Online Access: | https://doi.org/10.1186/s13041-022-00902-1 |
| _version_ | 1818329727044157440 |
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| author | Daisuke Sato Yusuke Hamada Michiko Narita Tomohisa Mori Hiroyuki Tezuka Yukari Suda Kenichi Tanaka Sara Yoshida Hideki Tamura Akihiro Yamanaka Emiko Senba Naoko Kuzumaki Minoru Narita |
| author_facet | Daisuke Sato Yusuke Hamada Michiko Narita Tomohisa Mori Hiroyuki Tezuka Yukari Suda Kenichi Tanaka Sara Yoshida Hideki Tamura Akihiro Yamanaka Emiko Senba Naoko Kuzumaki Minoru Narita |
| author_sort | Daisuke Sato |
| collection | DOAJ |
| description | Abstract Recent research has suggested that the mesolimbic dopamine network that mainly terminates in the nucleus accumbens may positively control the peripheral immune system. The activation of dopamine receptors in neurons in the nucleus accumbens by the release of endogenous dopamine is thus expected to contribute to efferent immune regulation. As in the stimulation of Gs-coupled dopamine D1-receptors or Gi-coupled D2-receptors by endogenous dopamine, we investigated whether specific stimulation of dopamine D1-receptor-expressing neurons or inhibition of dopamine D2-receptor-expressing neurons in the nucleus accumbens could produce anti-tumor effects and improve the immune system in transgenic mice using pharmacogenetic techniques. Repeated stimulation of D1-receptor-expressing neurons in either the medial shell, lateral shell or core regions of the nucleus accumbens significantly decreased tumor volume under a state of tumor transplantation, whereas repeated suppression of D2-receptor-expressing neurons in these areas had no effect on this event. The number of splenic CD8+ T cells was significantly increased following repeated stimulation of D1-receptor-expressing neurons in the nucleus accumbens of mice with tumor transplantation. Furthermore, this stimulation produced a significant reduction in the population of splenic CD8+ T cells that expressed immune checkpoint-related inhibitory receptors, PD-1, TIM-3 and LAG-3. These findings suggest that repeated stimulation of D1-receptor-expressing neurons (probably D1-receptor-expressing medium spiny neurons) in the nucleus accumbens suppressed tumor progression and improved the immune system by suppressing the exhaustion of splenic CD8+ T cells. |
| first_indexed | 2024-12-13T12:52:39Z |
| format | Article |
| id | doaj.art-0a1388f452bf4dafba3827ad0184455c |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-13T12:52:39Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-0a1388f452bf4dafba3827ad0184455c2022-12-21T23:45:17ZengBMCMolecular Brain1756-66062022-02-0115111310.1186/s13041-022-00902-1Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbensDaisuke Sato0Yusuke Hamada1Michiko Narita2Tomohisa Mori3Hiroyuki Tezuka4Yukari Suda5Kenichi Tanaka6Sara Yoshida7Hideki Tamura8Akihiro Yamanaka9Emiko Senba10Naoko Kuzumaki11Minoru Narita12Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical SciencesDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical SciencesDivision of Cancer Pathophysiology, National Cancer Center Research Institute (NCCRI)Department of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical SciencesDepartment of Cellular Function Analysis, Research Promotion and Support Headquarters, Fujita Health UniversityDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical SciencesDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical SciencesDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical SciencesInstitute for Advanced Life Sciences, Hoshi University School of Pharmacy and Pharmaceutical SciencesDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya UniversityDepartment of Physical Therapy, Osaka Yukioka College of Health ScienceDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical SciencesDepartment of Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical SciencesAbstract Recent research has suggested that the mesolimbic dopamine network that mainly terminates in the nucleus accumbens may positively control the peripheral immune system. The activation of dopamine receptors in neurons in the nucleus accumbens by the release of endogenous dopamine is thus expected to contribute to efferent immune regulation. As in the stimulation of Gs-coupled dopamine D1-receptors or Gi-coupled D2-receptors by endogenous dopamine, we investigated whether specific stimulation of dopamine D1-receptor-expressing neurons or inhibition of dopamine D2-receptor-expressing neurons in the nucleus accumbens could produce anti-tumor effects and improve the immune system in transgenic mice using pharmacogenetic techniques. Repeated stimulation of D1-receptor-expressing neurons in either the medial shell, lateral shell or core regions of the nucleus accumbens significantly decreased tumor volume under a state of tumor transplantation, whereas repeated suppression of D2-receptor-expressing neurons in these areas had no effect on this event. The number of splenic CD8+ T cells was significantly increased following repeated stimulation of D1-receptor-expressing neurons in the nucleus accumbens of mice with tumor transplantation. Furthermore, this stimulation produced a significant reduction in the population of splenic CD8+ T cells that expressed immune checkpoint-related inhibitory receptors, PD-1, TIM-3 and LAG-3. These findings suggest that repeated stimulation of D1-receptor-expressing neurons (probably D1-receptor-expressing medium spiny neurons) in the nucleus accumbens suppressed tumor progression and improved the immune system by suppressing the exhaustion of splenic CD8+ T cells.https://doi.org/10.1186/s13041-022-00902-1 |
| spellingShingle | Daisuke Sato Yusuke Hamada Michiko Narita Tomohisa Mori Hiroyuki Tezuka Yukari Suda Kenichi Tanaka Sara Yoshida Hideki Tamura Akihiro Yamanaka Emiko Senba Naoko Kuzumaki Minoru Narita Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbens Molecular Brain |
| title | Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbens |
| title_full | Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbens |
| title_fullStr | Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbens |
| title_full_unstemmed | Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbens |
| title_short | Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbens |
| title_sort | tumor suppression and improvement in immune systems by specific activation of dopamine d1 receptor expressing neurons in the nucleus accumbens |
| url | https://doi.org/10.1186/s13041-022-00902-1 |
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